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高效生物合成次黄嘌呤及其嘌呤代谢的转录组分析。

Highly Efficient Biosynthesis of Hypoxanthine in and Transcriptome-Based Analysis of the Purine Metabolism.

机构信息

CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Siences, Qingdao, 266101, China.

出版信息

ACS Synth Biol. 2020 Mar 20;9(3):525-535. doi: 10.1021/acssynbio.9b00396. Epub 2020 Feb 21.

Abstract

Nucleosides and purine analogues have multiple functions in cell physiology, food additives, and pharmaceuticals, and some are produced on a large scale using different microorganisms. However, biosynthesis of purines is still lacking. In the present study, we engineered the purine biosynthesis pathway, branched pathways, and a global regulator to ensure highly efficient hypoxanthine production by . The engineered strain Q2973 produced 1243 mg/L hypoxanthine in fed-batch fermentation, accompanied by an extremely low accumulation of byproducts such as acetate and xanthine. We also performed global gene expression analysis to illustrate the mechanism for improving hypoxanthine production. This study demonstrated the feasibility of large-scale hypoxanthine production byan engineered . strain, and provides a reference for subsequent studies on purine analogues and nucleosides.

摘要

核苷和嘌呤类似物在细胞生理学、食品添加剂和药物方面具有多种功能,其中一些使用不同的微生物大规模生产。然而,嘌呤的生物合成仍然缺乏。在本研究中,我们通过工程化嘌呤生物合成途径、分支途径和全局调控因子来确保 通过 高效生产次黄嘌呤。工程菌株 Q2973 在分批补料发酵中产生了 1243mg/L 的次黄嘌呤,同时副产物如乙酸盐和黄嘌呤的积累极低。我们还进行了全局基因表达分析,以阐明提高次黄嘌呤产量的机制。本研究证明了 通过工程化 菌株大规模生产次黄嘌呤的可行性,为随后嘌呤类似物和核苷的研究提供了参考。

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